N-donor complexes of palladium as catalysts for Suzuki cross-coupling
reactions in ionic liquids.
Christopher J. Mathews,a Paul J. Smithb and Tom Weltonb
a
Syngenta, Jealotts International Research Centre, Bracknell, UK RG42 6ET.
b
Department of Chemistry, Imperial College of Science Technology and Medicine,
London, UK SW7 2AY.
E-mail: t.welton@ic.ac.uk
Abstract
Palladium imidazole complexes have been used as catalyst precursors for the Suzuki
cross-coupling reaction in 1-butyl-3-methylimidazolium-based ambient temperature
ionic liquids. The system provides a stable, recyclable method for iodo- and
bromoarenes. The preferred reaction conditions are explored and the effect of
changing the ionic liquid components is investigated.
Introduction
Palladium catalysed coupling and cross-coupling reactions remain a method of choice
for the formation of C-C bonds. Recent developments have led to the activation of
aryl chlorides,1 and room temperature catalysis.2 Significant innovations have been
made in the discoveries of novel phosphine systems and in the modification of
traditional phosphines. The replacement of the commonly used triarylphosphine
ligands with sterically-hindered and electron-rich trialkylphosphines,3 phosphites,4
and phospha-palladacycles5 have all given rise to highly active systems in palladium
catalysed coupling reactions.
Our interest has been in the use of ionic liquids as solvents for the Suzuki
reaction.6 The application of ionic liquids as solvents for transition metal catalysis is
an area of intense interest,7 and a wide range of processes are under investigation. The
first reported example of a palladium catalysed coupling reaction in an ionic liquid
was the Heck reaction in phosphonium and ammonium based ionic liquids.8 Since
then, palladium catalysed coupling reactions have become one of the most active
areas of catalyst research in ionic liquids.9 To date, we have reported the use of
various palladium sources, either with phosphine ligands or added phosphines.
However, unexpected activity observed during control experiments led us to
investigate the use of palladium complexes of N-donor ligands as catalysts in ionic
liquids. It is this work that we report here.
The use of N-coordinated ligands in palladium catalysed coupling reactions
has been an area of limited activity. Most examples involve cyclometallated
palladium complexes incorporating either the imine,10,11 amine,12 oxime,13 or
oxazoline14 moieties. The remainder include either chelating bi- or terdentate Ncoordinating ligands such as diazabutanes,15,16 bis(oxazolinyl)pyrrole17 or dipyridyl18
ligands, respectively. A series of methyl palladium(II) complexes have also been
reported, incorporating N-coordinated bis- and tris-imidazole chelates that were found
to be catalytically active in the Heck reaction of 4-bromoacetophenone with n-butyl
acrylate.19 Recently, an example of a mixed imidazolylidene-imidazole palladium
complex and its application in Sonogashira coupling reactions has been reported.20
We have reported the use of palladium(II) imidazole based complexes in molecular
solvents as catalysts for the Suzuki reaction.21
Br
B(OH) 2
(CH3CN)PdCl2
N-donor ligand
Na2CO3 (aq)
+
Ionic Liquid
Scheme 1. The Suzuki coupling reaction of a bromobenzene with tolylboronic acid
Results and discussion
While searching for soluble sources of palladium for the palladium/phosphine
catalysed
Suzuki
reactions
in
ionic
liquids
the
tetrachloropalladate
salt,
[C4C1im]2[PdCl4]* was investigated. Its use in combination with triphenylphosphine
in [C4C1im][BF4], gave an active system for the reaction of bromobenzene and
tolylboronic acid (Table 1), with a 65.8% yield of 4-methylbiphenyl in 20 min at 110
C without any apparent catalytic decomposition. This was typical of several of the
palladium sources that we used in this reaction. However, unlike the other palladium
sources used, which were inactive in the absence of PPh3, the use of [C4C1im]2[PdCl4]
alone gave rise to a 45.3% yield of 4-methylbiphenyl in 20 min (Table 1). Extensive
catalyst decomposition was evident. [C4C1im]2[PdCl4] has also been reported to act as
a catalyst for the Heck reaction in [C4C1im][PF6].22
Table 1. The Suzuki reaction of bromobenzene and tolylboronic acid in
[C4C1im][BF4] with a variety of palladium sources.
Palladium source
Yield a
(%)
TON h−1 b
Homo c
(%)
[C4C1im]2[PdCl4]
45.3 d
113
3.7
[C4C1im]2[PdCl4]/4PPh3
65.8
165
2.9
Pd(PPh3)46
68.2
171
2.1
Conditions: 1.2 mol% catalyst, Temp = 110 ˚C, time = 20 mins. a Isolated yields of 4-methylbiphenyl,
based on bromobenzene. b TON h−1 = number of moles of desired product per mole of catalyst used per
hour. c Homo-coupled 4,4’-dimethylbiphenyl yield. d Extensive catalyst decomposition and leaching.
*
Note on nomenclature. The substituted imidazolium cations used in this paper are abbreviated to
[CnCn’im]+, where n and n’ are the chain lengths of the respective alkyl chains. For example, [C4C1im]+
is the 1-butyl-3-methylimidazolium cation.
Palladium(II) salts have previously been reported to catalyse coupling
reactions without added ligands, although long reaction times are generally required.23
However, [C4C1im]2[PdCl4] has been previously reported as a palladium source for
the hydrodimerisation of 1,3-butadiene in both [C4C1im][BF4] and [C4C1im][PF6].24
Here it was claimed that the active species was (mim)2PdCl2 generated in situ from a
reaction of the [C4C1im]2[PdCl4] with the ionic liquids. This led us to test the
possibility that a similar chain of events was occurring in our Suzuki reactions,
leading to palladium/imidazole complexes that act as catalysts, or their immediate
precursors, in these ionic liquids.
ESI mass spectra of a solution of [C4C1im]2[PdCl4] in dry [C4C1im][BF4]
revealed peaks attributable only to the [C4C1im]2[PdCl4] {[(C4C1im)2PdCl3]+, 491 Da;
[(C4C1im)3PdCl4]+, 667 Da; [(C4C1im)4PdCl5]+, 842 Da} and the ionic liquid itself,
even after four weeks stored under N2. However, upon addition of water the ESI MS
revealed a new peak at 307 Da, corresponding to [(mim)2PdCl]+. This confirmed the
formation of (mim)2PdCl2 in the ionic liquid and that its formation is not due to 1methylimidazole impurities in the ionic liquid. In our Suzuki reactions NaCO3 is
added as an aqueous solution, so giving conditions for the potential formation of
(mim)2PdCl2. Hence, we chose to investigate the use of palladium/imidazole catalysts
for the Suzuki reaction in ionic liquids.
Initial experiments, with 1-methylimidazole to determine the reaction
conditions to be used found that the addition of (CH3CN)2PdCl2 and 1methylimidazole directly to the ionic liquid was the preferable method for the
introduction of the catalyst. The solutions where then heated to 110 ˚C, during which
time the yellow colour of the palladium faded. Performing the Suzuki reaction
without this prior heating of the (CH3CN)2PdCl2/4mim {where mim = 1methylimidazole} in the [C4C1im][BF4] resulted in decomposition of the catalyst
during the reaction and a decreased yield of 4-methylbiphenyl. Thus, as with the
palladium/phosphine catalytic system that we have previously reported,6 the initiation
of the catalyst was fundamental to the success of the ionic liquid mediated Suzuki
reaction. The resulting solution was cooled to room temperature, the aqueous Na2CO3
solution and the starting materials added and the reaction carried out at 110 C for 20
min. In contrast to the palladium/phosphine system, the catalyst preparation in the
ionic liquid could be conducted under air, without any detrimental effect on the
eventual Suzuki reaction.
It was found that, in order to prevent catalyst decomposition, at least 4
equivalents of 1-methylimidazole were required, relative to the palladium, whilst
more than 4 equivalents inhibited the reaction. Using 4 equivalents of 1methylimidazole the reaction had reached its maximum yield after 1 h at 110 C,
achieving a 83.3% yield, with only a marginal increase after 3 h (Table 2). The
reaction could also be performed at room temperature, achieving a 78.7% yield in 24
h. Unreacted bromobenzene was detected at the end of all the reactions and less than a
4% yield of 4,4′-dimethylbiphenyl was generated from homo-coupling.
Table 2. Investigation of reaction conditions (CH3CN)2PdCl2/4mim catalysed Suzuki
reactions.
Time
Reaction
Yield a TON h−1 b Homo c
(%)
(%)
temperature (C)
20 min
1h
3h
24 h
110
110
110
25
42.4
83.3
86.1
78.7
106
69
24
3
3.3
2.0
3.8
2.9
Conditions: 1.2 mol% catalyst, L:cat = 4:1.a Isolated yields of 4-methylbiphenyl product, based on
bromobenzene. b TON h−1 = number of moles of desired product per mole of catalyst used per hour. c
Homo-coupled 4,4’-dimethylbiphenyl product.
Comparison with molecular solvents
We have reported the reaction of bromobenzene and tolylboronic acid in molecular
solvents previously (Table 3).21 It can be seen immediately that the reaction yields and
turnover numbers are greater in most of the molecular solvents used. The only
exception to this is THF, which due to its boiling point operates at a significantly
lower temperature with an associated reduction in rate. It is also noticeable that the
reaction in molecular solvents leads to no homo-coupled product being formed.
However, in all of these solvents the catalyst was seen to decompose and after
extraction it was not possible to repeat the reaction.
Only in the ionic liquid was it possible to recycle and reuse the reaction
system. The reaction in [C4C1im][BF4] was, therefore, repeated. After washing with
hexane to remove the products the solution was further washed with aliquots of water
until a single phase was formed on addition of the aliquot. The ionic liquid was then
dried and fresh base and starting materials added. It can be seen (Table 3) that the
ionic liquid provided a stable reaction system for the reaction, with no significant loss
in activity.
Clearly there are two regimes, the first is highly active, but unstable, the
second is less active, but very stable. We have previously invoked the formation of
palladium/imidazolylidene complexes in [C4C1im]+ ionic liquids to explain the
reactivity of palladium/phosphine mixtures in ionic liquids.6 It is possible that
analogous mixed imidazolylidene/imidazole catalysts are being formed in this
reaction.
Table 3. The reaction of bromobenzene and tolylboronic acid in a variety of solvents
Solvent
Yield a
(%)
TON h−1 b
Homo c
(%)
[C4C1im][BF4] run 1
[C4C1im][BF4] run 2
[C4C1im][BF4] run 3
[C4C1im][BF4] run 4
[C4C1im][BF4] run 5
42.4
45.4
43.2
40.7
42.9
106
114
108
102
107
3.3
3.8
2.5
3.2
2.7
dioxane21
toluene21
THF (60 ˚C)21
Water (100 ˚C)21
95.7 d
89.8 d
36.8 d
92.8 d
239
225
92
232
0
0
0
0
Conditions: 1.2 mol% catalyst, L:cat = 4:1, Temp = 110 ˚C, time = 20 mins. aIsolated yields of 4methylbiphenyl product, based on bromobenzene. b TON h−1 = number of moles of desired product per
mole of catalyst used per hour.
c
Homo-coupled tolylboronic acid yield.
d
Yellow−orange solution
afforded from the initiation process. Extensive catalyst decomposition and leaching.
The ESI-MS catalytic investigation in [C4C1im][BF4]
In order to confirm the reason for the stability of the catalyst system in the ionic
liquids, we investigated the species formed in solution with ESI-MS. When
(CH3CN)2PdCl2 and 1-methylimidazole were added to the [C4C1im][BF4] and heated
at 110 C for 1 h under N2 the ESI-MS revealed signals at 387 {[(mim)3PdCl]+}, 371
{unidentified Pd complex}, 346 {unidentified Pd complex}, 270 {[(mim)2Pd]+} and
83 {[Hmim]+} m/z. Upon addition of aqueous sodium carbonate and reheating of the
solution a new signal at 443 {[(mim)2Pd(C4C1imy)Cl]+} (where C4C1imy = 1-butyl-3methylimidazolylidene)
appeared.
This
provides
evidence
that
mixed
imidazolylidene/1-methylimidazole palladium complexes could be generated in situ
under conditions similar to those used in catalytic reactions. However, it should be
stressed that, unlike the phosphine system, other palladium containing signals are
present, some of which are unidentified, that may result from other species that could
be
catalysing
the
reaction.
Attempts
to
independently
prepare
the
[(mim)2Pd(C4C1imy)Cl]+ complex were unsuccessful.
Variation of ionic liquid-cation effect
If the formation of palladium/imidazolylidene complexes is important in the catalysis,
it would be expected that there would be a significant effect of changing the cation of
the ionic liquid on the reaction. Hence, a study of the effect of different ionic liquids
on the Suzuki reaction of bromobenzene with tolylboronic acid was performed with
the (CH3CN)2PdCl2/4mim system (Table 4).
Table 4. Scope of the Suzuki reaction with different ionic liquids – cation effects
Solvent
Yield a
(%)
TON h−1 b
Homo c
(%)
[C2C1im][BF4]
[C4C1im][BF4]
[C6C1im][BF4]
[C4C4im][BF4]
18.8
42.4
32.4
55.5
47
100
81
139
1.7
2.7
2.0
3.2
[C4C1C1im][BF4]
[C4C1py][N(SO2CF3)2]
85.3 d
83.4 d
213
209
1.4
4.1
Conditions: 1.2 mol% catalyst, L:cat = 4:1, Temp = 110 ˚C, time = 20 mins. aIsolated yields of 4methylbiphenyl product, based on bromobenzene. b TON h−1 = number of moles of desired product per
mole of catalyst used per hour.
c
Homo-coupled tolylboronic acid yield.
d
Yellow−orange solution
afforded from the initiation process. Extensive catalyst decomposition and leaching.
The first thing to notice is that the two ionic liquids for which imidazolylidene
formation is not possible {[C4C1C1im][BF4] (where bmmim = 1butyl-2,3dimethylimidazolium) and [C4C1py][N(SO2CF3)2] (where bmpy = 1-butyl-1methylpyrolidimum)} give the highest yielding reactions and extensive catalyst
decomposition. These ionic liquids generated a yellow−orange solution after the
initiation of the catalyst, rather than the colourless solution formed by the lower
yielding, but stable catalyst solutions. Analogy with the previously reported
palladium/phosphine systems6 in ionic liquids suggests that the catalyst stability in the
ionic liquids is generated by the ability of the imidazolium ions to form
imidazolylidene ligands with the palladium. However, unlike the phosphine systems,
the ionic liquids in which palladium/imidazolylidene complexes cannot be formed
give more reactive catalysts, with reactivities similar to that found in molecular
solvents (see above). There is no obvious trend in the reactivities in the ionic liquids
that can form imidazolylidene ligands.
Variation of ionic liquid-anion effect
The effect of the anion in 1-butyl-3-methyl imidazolium ionic liquids is less clear than
that of the cation. Stable catalyst systems were formed in all of these ionic liquids.
The highest yields were achieved in the [C4C1im][OSO2CF3] and [C4C1im][PF6],
(Table 5). [C4C1im][N(SO2CF3)2] and [C4C1im][BF4] gave lesser yields with
[C4C1im][OSO2CH3] and [C4C1im]Cl giving no yield at all.
It has been shown that the basicity of the anions of the ionic liquid can affect
the electrophilicity of transition metal centres.25 The greater the basicity the stronger
is the interaction with the metal centre and the slower the reaction. However, although
this may be contributing to the observed reactivities here it cannot be the complete
explanation. While it offers an explanation for the other ionic liquids, under this
argument the reactivities of the [N(SO2CF3)2]− and the [OSO2CF3]− liquids would be
expected to be reversed. We are continuing to investigate this phenomenon.
Table 5. Scope of the Suzuki reaction with different ionic liquids – anion effect
Solvent
Yield a TON h−1 b Homo c
(%)
(%)
[C4C1im][BF4]
[C4C1im][PF6]
[C4C1im][N(SO2CF3)2]
[C4C1im][OSO2CF3]
[C4C1im]Cl
[C4C1im]Br
[C4C1im][OSO2CH3]
42.4
59.5
36.4
62.4
0
24.9
0
100
150
90
156
0
63
0
2.7
2.3
3.3
1.8
0
1.3
0
Conditions: 1.2 mol% catalyst, L:cat = 4:1, Temp = 110 ˚C, time = 20 mins. aIsolated yields of 4methylbiphenyl product, based on bromobenzene. b TON h−1 = number of moles of desired product per
mole of catalyst used per hour. c Homo-coupled tolylboronic acid yield.
Variation of imidazoles and other N-donor ligands
The Suzuki reaction of bromobenzene with tolylboronic acid, in a 1:1 ratio, was
investigated with (CH3CN)2PdCl2 and a small number of other potential N-donor
ligands at 110 C for 20 min (Tables 6 and 7). Under these conditions a 42.4% 4methylbiphenyl yield was obtained, when 1-methylimidazole was used as a ligand,
which was approximately in the middle of the affordable yield range (0−80%).
Assuming other imidazoles exhibited similar activities, these conditions allowed the
widest window to observe any improvements or deteriorations. Furthermore, it
suggested some information about the reaction rates, as estimated by TON h−1, for the
different catalysts due to the presence of unreacted bromobenzene and absence of
catalyst decomposition at the end of the reaction period.
Table 6. Suzuki reactions with different imidazoles in [C4C1im][BF4]
Ligand
Yield a
(%)
TON h−1 b
Homo c
(%)
imidazole
2-methylimidazole
2-phenylimidazole
benzimididazole
2-methylbenzimidazole
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1-methylimidazole
1-butylimidazole
1-phenylimidazole
1-methylbenzimidazole
42.4
40.2
76.0
88.2
100
101
190
221
2.7
3.6
2.5
3.7
1,2-dimethylimidazole
1-butyl-2-methylimidazole
1,2,4,5-tetramethylimidazole
1-methyl-2-phenylimidazole
1-butyl-2-phenylimidazole
31.2
33.9
29.2
32.4
28.9
78
85
73
81
72
1.5
3.0
2.2
3.2
2.2
Conditions: 1.2 mol% catalyst, L:cat = 4:1, Temp = 110 ˚C, time = 20 mins. a Isolated yields of 4methylbiphenyl product, based on bromobenzene. b TON h−1 = number of moles of desired product per
mole of catalyst used per hour. c Homo-coupled tolylboronic acid yield.
Imidazoles incorporating an N−H bond gave no Suzuki cross-coupled product
and
unreacted
bromobenzene
was
detected
(Table
6).
The
‘ligandless’
{(CH3CN)2PdCl2} catalytic system gave a 25.4% 4-methlybiphenyl yield and,
therefore, these imidazoles must be actively inhibiting the Suzuki reaction.
Different N-alkyl substituents had no effect on the yield, for example, 1butylimidazole gave a comparable yield to 1-methylimidazole (Table 6). However, 1phenylimidazole gave a yield of 76.0% under these conditions and 1methylbenzimidazole was found to be the most active imidazole based systems tested
(88.2% yield).
C-2 substitution of the imidazoles led to a reduction in the yield in
comparison to the parent imidazole, irrespective of the nature of the C-2 substituent.
For example, 1-butyl-2-phenylimidazole afforded a comparable yield to 1,2dimethylimidazole
Table 7. Scope of Suzuki reactions with other potential N-coordinated ligand
Ligand
Yield a
(%)
TON h−1 b
Homo c
(%)
pyrazole
tetrazole
0
0
0
0
0
0
DBU
15.2
38
1.1
4-methylthiazole
pyridine
Et3N
1,4-bis-(diisopropylphenyl)-1,3diazabutadiene
2,2′-bipyridyl
81.2 d
75.4 d
79.0 d
203
189
200
2.0
3.4
2.6
92.3 d
231
3.1
68.2 d
171
1.9
Conditions: 1.2 mol% catalyst, L:cat = 4:1, Temp = 110 ˚C, time = 20 mins.
a
Isolated yields of 4-
methylbiphenyl product, based on bromobenzene. b TON h−1 = number of moles of desired product per
mole of catalyst used per hour.
c
Homo-coupled tolylboronic acid yield.
d
Yellow−orange solution
afforded from the initiation process. Extensive catalyst decomposition observed during reaction.
Other N-donor ligands were also investigated (Table 7). The inhibiting nature
of N−H bonds were also observed for pyrazole and tetrazole ligands (Table 7). Other
N-coordinating ligands tested were shown to be highly active, albeit with extensive
decomposition. This would suggest that the nature of the N-donor ligand is important
in
determining
whether
a
palladium/imidazolylidene
complex
can
form.
Diazabicycloundecene (DBU) was found to produce a 15.2% yield of 4methylbiphenyl with no decomposition.
The N-bidentate ligands, 1,4-bis-(diisopropylphenyl)-1,3-diazabutadiene and
2,2′-bipyridyl, investigated by Nolan15 were also examined in [C4C1im][BF4] (Table
7). These catalytic systems performed significantly better in the ionic liquid than in
dioxane, in which 80 and 13% yields were reported for the diazabutadiene and
bipyridyl ligands, respectively. However, catalyst decomposition was clearly
observed.
Conclusions
A number of substituted imidazoles, when used with palladium(II) sources in ionic
liquids, provide a robust air-stable system for Suzuki reactions. A successful Suzuki
reaction required the initiation of the catalytic system in the ionic liquid prior to the
reaction. This was achieved by heating the palladium source with the imidazole in the
ionic liquid to generate a completely colourless catalytic solution. Without the
initiation low yields were obtained with catalytic decomposition. The catalytic
activity and stability in the ionic liquids was strongly dependent on the nature of the
imidazole ligands and on the natures of the anion and cation of the ionic liquid. The
(CH3CN)2PdCl2/4mim catalytic system was found to be highly active in
[C4C1py][N(SO2CF3)2], [C4C1C1im][BF4] and molecular solvents, although extensive
catalyst decomposition occurred.
The reactivities of the different solutions that were stable depend on both the
cation and the anion of the ionic liquid, the most active of those tested being
[C4C1im][PF6] and [C4C1im][OSO2CF3]. It has also been shown that it is possible to
use the imidazole ligand to improve reactivities, with 1-phenylimidazole and 1methylbenzimidazole giving the most active catalysts in [C4C1im][BF4]. Hence there
is a great deal if synthetic flexibility that can be explored in to improve upon and
develop this new catalyst system.
Experimental
General
Unless otherwise stated, all materials were used as obtained without further
purification. Acetonitrile, CH2Cl2, dioxane and ethyl acetate were distilled from CaH2,
The ionic liquids were prepared using methods that we have previously described.26
The imidazoles were freshly distilled from KOH under reduced pressure, as were 3methylthiazole, DBU, pyridine and triethylamine. Pyrazole and tetrazole were
recrystallised from CHCl3 and hexane. NMR spectra were recorded on a JEOL GSX270 FT spectrometer. ESI-MS were performed on a Waters HPLC 600 with a
micromass ZMD (capillary 3.64 kV; cone = 31 V; extractor = 8 V; source temp. 100
C and desolvation temp. = 120 C). GC analysis were performed with a Hitachi 163
gas chromatograph using a 2 m  3 mm carbowax column.
Preparation of bis-(acetonitrile)dichloropalladium(II), (CH3CN)2PdCl2
A suspension of PdCl2 (2.00 g, 11.3 mmol) was heated at reflux in CH3CN (100 cm3)
with vigorous stirring for 18 h under N2. Hot filtration of the resultant wine-red
coloured solution through a celite pad into stirred petroleum spirit (40−60 C; 100
cm3) at ambient temperature gave a yellow−orange solid. Recrystallisation from a
CH3CN (200 cm3), CH2Cl2 (300 cm3) and hexane (100 cm3) mixture gave
(CH3CN)2PdCl2 (1.78 g, 65.3%) as a bright yellow powdery solid; mp 129−131 C
(decomp); Found: C, 18.63; H, 2.27; N, 10.77; C4H6N2Cl2Pd requires C, 18.55; H,
2.33; N, 10.82%; max(KBr)/cm−1 3285, 2979, 2918, 2338, 1412, 1329, 1022, 959,
438 and 407; H(270 MHz, d6-DMSO) / ppm 2.06 (6H, s, 2CH3); C(68 MHz, d6DMSO) / ppm 118.0 (s, CH3CN) and 1.09 (s, CH3CN).
A typical Suzuki reaction in ionic liquid
To a flask charged with [C4C1im][BF4] (1.6 cm3) was injected (CH3CN)2PdCl2 (2.36
mg, 9.12 mol, 1.2 mol%) and 1-methylimidazole (3.00 mg, 36.5 mol, 4.8 mol%)
The yellow solution was stirred at 110 C for 1 h under N2, during which time the
colour disappeared. The flask was then removed from the heat and allowed to cool to
ambient temperature. To the colourless solution Na2CO3 (161 mg, 1.52 mmol, 2 eq.)
in deoxygenated water (0.80 ml), bromobenzene (119.3 mg (80.00 L), 0.7597 mmol,
1 eq.) and the tolylboronic acid (114 mg, 0.837 mmol, 1.1 eq.) was added. The
solution was then heated to 110 C for 20 min. At that point the flask was rapidly
cooled in a dry-ice/acetone bath (-78 C), the reaction mixture was diluted with water
(2 ml) and extracted with hexane (4  15 cm3). The extracts were washed with brine
(3  40 ml) and water (3  40 ml), filtered through a pad of silica and evaporated to
dryness to afford 4-methylbiphenyl (51.0 mg, 42.4%) as a colourless crystalline solid.
Acknowledgements
We would like to thank the EPSRC and Syngenta for the provision of a CASE award
(PJS). We would also like to thank the editors of this special edition for the invitation
to submit this paper.
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3
a) A. F. Littke, C. Dai and G. C. Fu, J. Am. Chem. Soc., 2000, 122, 4020−4028; b) A. F. Littke and G.
C. Fu, J. Org. Chem., 1999, 64, 10−11; c) J. P. Wolfe, R. A. Singer, B. H. Yang and S. L. Buchwald, J.
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A. Zapf and M. Beller, Chem. Eur. J., 2000, 6, 1830−1833.
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For a review see: W. A. Herrmann, V. P. W. Böhm and C. Reisinger, J. Organometallic Chemistry,
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a) C. Mathews, P. J. Smith and T. Welton, Chem. Commun., 2000, 1249-1250; b) C. Mathews, P. J.
Smith, T. Welton, A. J. P. White, D. J. Williams, Organometallics., 2001, 20, 3848-3850; c) C.
Mathews, P. J. Smith and T. Welton, Organometallics, 2003, in press
7
a) P. Wasserscheid and W. Keim, Angew. Chem. Int. Ed. Engl., 2000, 39, 3772−3789; b) H. OlivierBourbigou and L. Magna, J. Mol. Catal. A: Chem., 2002, 182, 419−437; c) R. Sheldon, Chem.
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Rev., I999, 99, 2071-2084; f) Ionic Liquids in Synthesis, P. Wasserschied and T. Welton (eds.), VCH
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D. E. Kaufmann, M. Nouroozian and H. Henze, Synlett, 1996, 1091−1092.
9
Some examples: a) K. Okubo, M. Shirai, C. Yokoyama, Tetrahedron Lett., 2002, 43,7115; b) K.
Selvakumar, A. Zapf, M. Beller, Org. Lett., 2002, 4, 3031; c) K. S. A. Vallin, P. Emilsson, M. Larhed,
A. Hallberg, J. Org. Chem., 2002, 67, 6243; d) T. Fukuyama, M. Shinmen, S. Nishitani, M. Sato, I.
Ryu, Org. Lett., 2002, 4,1691; e)R. Rajagopal, D. V. Jarikote, K. V. Srinivasan, Chem. Commun.,
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Shimizu, T. Hoshi, T. Suzuki, M. Ando, K. Ohkubo, C. Yokoyama, Tetrahedron Lett., 2001, 42, 4349;
h) L. J. Xu, W. P. Chen, J. Ross, J. L. Xiao, Org. Lett., 2001, 3, 295; i) V. P. W. Bohm, W. A.
Herrmann, Chem.-Eur. J., 2000, 6, 1017; j) A. J. Carmichael, M. J. Earle, J. D. Holbrey, P. B.
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a) M. Ohff, A. Ohff and D. Milstein, Chem. Commun., 1999, 357−358; b) H. Weissman and David
Milstein, Chem. Commun., 1999, 1901−1902.
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a) D. A. Alonso, C. Nájera and M. C. Pacheco, Org. Lett., 2000, 2, 1823−1826; b) S. Iyer and C.
Ramesh, Tetrahedron. Lett., 2000, 41, 8981−8984; c) S. Iyer and A. Jayanthi, Tetrahedron. Lett.,
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F. Yang, Y. Zhang, R. Zheng, J. Tang and M. He, J. Organ met. Chem., 2002, 651,146 −148.
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(a) L. Botella and C. Nájera, Angew. Chem. Int. Ed., 2002, 41, 179-181; (b) L. Botella and C. Nájera,
J. Organomet. Chem., 2002, 663, 46-57.
14
B. Tao and D. W. Boykin, Tet. Lett., 2002, 43, 4955−4957.
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G. A. Grasa, A. C. Hillier and S. P. Nolan, Org. Lett., 2001, 3, 1077−1080.
16
A. S. Abu-Surrah, M. Kettunen, K. Lappalainen, U. Piironen, M. Klinga and M. Leskelä,
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17
C. Mazet and L. H. Gade, Organometallics., 2001, 20, 4144−4146.
18
M. R. Buchmeiser, T. Schareina, R. Kempe and K. Wurst, J. Organomet. Chem., 2001, 634, 39-46.
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a) M. C. Done, T. Rüther, K. J. Cavell, M. Kilner, E. J. Peacock, N. Brauusaud, B. W. Skelton and
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R. A. Batey, M. Shen and A. J. Lough, Org. Lett., 2002, 4, 1411−1414.
C. Mathews, P. J. Smith and T. Welton, J. Mol. Catal. A, 2003, 206, 77 – 82.
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A. J. Carmichael, M. J. Earle, J. D. Holbrey, P. B. McCormac and K. R. Seddon, Org. Lett., 1999, 1,
997−1000.
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a) M. T. Reetz, G. Lohmer and R. Schwickardi, Angew. Chem. Int. Ed., 1998, 37, 481−483; b) M. T.
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Chem., 2001, 1131−1133.
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J. E. L. Dullius, P. A. Z. Suarez, S. Einloft, R. F. de Souza, J. Dupont, J. Fischer and A. D. Cian,
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P. Wasserschied, C. M. Gordon, C. Hilgers, M. J. Muldoon and I. R. Dunkin, Chem. Commun.
2001,1186-1187
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S. G. Kazarian, P. Salter and T. Welton, Phys. Chem. Chem. Phys., 2001, 3, 5192 – 5200.
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